A periodontal barrier and method incorporating chemotherapeutic agents is disclosed for aiding and guiding periodontal tissue regeneration.

Patent
   5197882
Priority
May 14 1990
Filed
Feb 20 1992
Issued
Mar 30 1993
Expiry
May 14 2010
Assg.orig
Entity
Small
59
36
all paid
21. A periodontal barrier comprising:
a porous matrix made of a body compatible material and configured for aiding and guiding periodontal tissue growth adjacent a tooth; and
time-release microparticles encapsulating at least one chemotherapeutic agent being incorporated into said porous material by a process selected from the group consisting of extruding said microshapes into the microstructure of said barrier, weaving said microshapes into the microstructure of said barrier, mixing said microshapes with a fluid or gel and flowing them into the microstructure of said barrier, placing said microshapes between one or more layers of said barrier and positioning said microshapes between said barrier and an elastomer coating covering said barrier, wherein said time-release microparticles will begin to release said chemotherapeutic agent at a localized periodontal tissue regeneration site upon surgical implantation of said periodontal barrier.
1. A method for aiding and guiding periodontal tissue regeneration, comprising the steps of:
incorporating time-release microshapes encapsulating at least one chemotherapeutic agent into a biocompatible periodontal barrier so as to provide for sustained, controlled delivery of said at least one chemotherapeutic agent to a localized periodontal regeneration site in a mammalian body, said incorporating step is selected from the group consisting of extruding said microshapes into a microstructure of said barrier, weaving said microshapes into the microstructure of said barrier, mixing said microshapes with a fluid or gel and flowing them into the microstructure of said barrier, placing said microshapes between one or more layers of said barrier and positioning said microshapes between said barrier and an elastomer coating covering said barrier; and
implanting said barrier at said localized periodontal regeneration site, wherein said time-release microshapes will begin to release said at least one chemotherapeutic agent at said localized periodontal regeneration site in a sustained controlled manner.
2. The method of claim 1 wherein the incorporating step includes selecting a biocompatible barrier which is nonresorbable.
3. The method of claim 2 wherein said incorporating step includes selecting a biocompatible, nonresorbable barrier composed of a material selected from the group consisting of polytetrafluoroethylene, dacron, proplast and polypropylene.
4. The method of claim 1 wherein the incorporating step includes selecting a biocompatible barrier which is resorbable.
5. The method of claim 4 wherein the incorporating step includes selecting a bicompatible, resorbable barrier composed of cross-linked collagen.
6. The method of claim 1 wherein the incorporating step includes selecting microshapes selected from the group consisting of microspheres, microfibrils, microfibers, hollow microfibers and microsponges.
7. The method of claim 6 wherein the incorporating step includes selecting microspheres sized between approximately 10 to 700 microns in diameter or hollow microfibers having a cross-sectional diameter between approximately 100 to 1000 microns.
8. The method of claim 1 wherein the incorporating step includes selecting time-release microshapes encapsulating step chemotherapeutic agents which have time release values, thereby assuring generally continuous release of said chemotherapeutic agents over a predetermined period of time.
9. The method of claim 8 wherein the incorporating step includes mixing said chemotherapeutic agent with a polymer comprising said time-release microshape.
10. The method of claim 9 wherein the mixing step includes selecting a bicompatible, non-resorbable polymer.
11. The method of claim 9 wherein the mixing step includes selecting a biodegradable, resorbable polymer.
12. The method of claim 10 or 11 wherein the mixing step includes selecting the polymer from the group consisting of collagen, cellulosic polymers, ethylene vinyl acetate, methacrylate polymers, lactic glycolic acid polymers, polycaprolactone, polylactides, polystyrene, polycarbonate, polysulfone and polyurethane.
13. The method of claim 1 wherein the incorporating step includes selecting microshapes for incorporation into said barriers which are surrounded by a polymeric wall or shell, thereby providing for continuous or periodic release of said chemotherapeutic agents over a predetermined period of time.
14. The method of claim wherein the incorporating step includes selecting the chemotherapeutic agent from the group consisting of antibacterial, antibiotic, anti-inflammatory and tissue regenerative agents.
15. The method of claim 14 wherein the incorporating step includes selecting the antibacterial agent from the group consisting of bisbiguanides, fluorides, iodine, heavy metal salts and sulfonamides.
16. The method of claim 14 wherein the incorporating step includes selecting the antibiotic agent from the group consisting of vancomycin, tetracycline, penicillin, cephalosporins, erythromycin, metronidazole, neomycin and kanamycin.
17. The method of claim 14 wherein the incorporating step includes selecting the anti-inflammatory agent from the group consisting of steroidal anti-inflammatory agents and non-steroidal anti-inflammatory agents.
18. The method of claim 17 wherein the incorporating step includes selecting the steroidal anti-inflammatory agent from the group consisting of cortisone, hydrocortisone, beta-methasone, dexamethasone and prednisolone.
19. The method of claim 17 wherein the incorporating step includes selecting the a non-steroidal anti-inflammatory agent from the group consisting of indomethacin, flurbiprofen, meclofenamic acid, ibuprofen and naproxen.
20. The method of claim 14 wherein the incorporating step includes selecting the tissue regenerative agent from the group consisting of fibronectin and bone morphogenic protein.

This is a continuation of application Ser. No. 07/522,999, filed May 14, 1990, which was abandoned upon the filing thereof.

The present invention relates to a periodontal barrier and method, and in particular, a periodontal barrier and method for aiding periodontal tissue regeneration.

Periodontal disease is a major concern in dentistry. Applicant's U.S. Pat. No. 4,685,883 deals with the treatment of periodontal and related diseases. Periodontal tissues are often lost with the progression of periodontal disease. Loss of periodontal tissue compromises the prognosis for retention of teeth in the dental arch, often creates an unhealthy environment in the mouth and may be unsightly.

Various methods have been used to facilitate regeneration of lost or diseased periodontal tissue. Periodontal barriers are sometimes surgically implanted adjacent the root of the tooth, or wherever tissue loss has occurred, by periodontal surgery to aid and guide tissue regeneration along the tooth surface where periodontal tissue regeneration is desired. Presently, these barriers are comprised of materials such as polytetrafluoroethylene (PTFE) which is biocompatible and non-resorbable. The barriers are typically removed after 4-6 weeks by a surgical re-entry procedure. Resorbable barriers are also being investigated for potential use in periodontal guided tissue regeneration. For example, cross-linked collagen is being studied in this regard.

It is often difficult to obtain the periodontal tissue growth desired since the regeneration of periodontal tissue is variable. Moreover, surgical implantation of barriers can be associated with infection and inflammation. Infection and excessive inflammation can adversely effect tissue regeneration with the use of periodontal barriers for guiding healing. Therefore it would be beneficial to be able to treat the tissue regeneration site with antibiotics, anti-inflammatories, or other appropriate chemotherapeutic agents as required to facilitate periodontal tissue regeneration. Presently, applicant is not aware of chemotherapeutic agents being incorporated into these barriers to facilitate tissue regeneration.

A potential problem envisioned with the use of chemotherapeutic agents in conjunction with periodontal barriers is how to control and regulate the delivery of such agents to the tissue regeneration site over an extended predetermined period of time so as to obtain the desired periodontal tissue growth.

The apparatus and method of the present invention solves these and many other problems associated with the use of periodontal barriers for tissue regeneration. The present invention provides a barrier and method wherein microparticles are incorporated into the periodontal barrier, the microparticles microencapsulating the chemotherapeutic agents desired.

The use of microparticles containing chemotherapeutic agents is known. For example, in Applicant's U.S. Pat. No. 4,685,883, time-release, microencapsulated chemotherapeutic agents are utilized to provide localized treatment of periodontal disease. However, the microcapsules are deposited in the periodontal pocket or attached to a root surface of the tooth for treatment of the periodontal disease itself and are not incorporated into a barrier for aiding or guiding periodontal tissue regeneration.

The present invention relates to a periodontal barrier and method providing for sustained, controlled delivery of microencapsulated chemotherapeutic agents, incorporated into the barrier, to a periodontal tissue regeneration site so as to aid and guide periodontal tissue regeneration.

An advantage of the present invention is to provide a periodontal tissue regeneration barrier incorporating microparticles microencapsulating chemotherapeutic agents, which upon implantation provide for sustained, controlled delivery of antibiotic, anti-inflammatory and other appropriate agents to the regeneration site, such that the barrier can aid and guide the regeneration of diseased or lost periodontal tissue.

One embodiment of the present invention will provide a periodontal barrier including one or more kinds of microencapsulated chemotherapeutic agent.

Yet another embodiment of the present invention will provide for release of different kinds of chemotherapeutic agents at different times.

Still another embodiment of the present invention will include a microencapsulated antibiotic and a microencapsulated anti-inflammatory.

These and various other advantages and features of novelty which characterize the invention are pointed out with particularity in the claims annexed hereto and forming a part hereof. However, for a better understanding of the invention, its advantages, and objects attained by its use, reference should be had to the drawings which form a further part hereof, and to the accompanying descriptive matter, in which there is illustrated and described a preferred embodiment of the invention.

In the drawings, in which like reference numerals and letters indicate corresponding parts throughout the several views,

FIG. 1 is a diagrammatic view of a periodontal barrier in accordance with the principles of the present invention positioned adjacent a tooth for aiding or guiding regeneration of periodontal tissue, the periodontal barrier incorporating time release microparticles encapsulating chemotherapeutic agents so as to provide controlled time release thereof;

FIGS. 2A through 2C are diagrammatic illustrations illustrating varying configurations of periodontal barriers;

FIG. 3 is a diagrammatic illustration illustrating a layer of the periodontal barrier being pulled back so as to reveal the microparticles contained in the periodontal barrier;

FIGS. 4A through 4D are end sectional views of periodontal barriers illustrating alternate embodiments of periodontal barriers showing various methods of incorporation of the microparticles into the periodontal barriers;

FIGS. 5A through 5D are diagrammatic perspective views of alternate configurations of the microparticles incorporated into the periodontal barrier and containing the chemotherapeutic agents;

FIGS. 6A through 6C are diagrammatic sectional views of alternate embodiments of microparticles having a somewhat spherical configuration with outside walls of vary thicknesses so as to provide for different timed release of chemotherapeutic agents from inside the microparticles; and

FIGS. 7A through 7D illustrate varying chemotherapeutic agent release patterns.

Referring now to FIG. 1, there is diagrammatically illustrated an embodiment of a periodontal barrier 20 surgically positioned adjacent a root 22 of a tooth 24 to aid and guide periodontal tissue 26 regeneration, including bone and periodontal ligament, of a periodontal defect 23 adjacent the root 22 of the tooth 24. Periodontal barriers 20 of varying configurations are illustrated in FIGS. 2A through 2C. In FIG. 3, an outer layer 28 of the periodontal barrier 20 is shown pulled away to illustrate incorporation of time release microparticles 30 encapsulating chemotherapeutic agents 32 so as to provide controlled time release thereof.

As noted, varying configurations of periodontal barriers, made of body compatible materials, including resorbable and nonresorbable materials, are illustrated in FIGS. 2A through 2C. These general configurations are commonly used in existing periodontal barriers. The specific configuration of the periodontal barrier used will depend on the anatomy of the tooth root(s), the periodontal defect and the growth that is desired. FIG. 2A illustrates a barrier which might be used with a narrow tooth. FIG. 2B illustrates a barrier which might be used with a wide tooth. FIG. 2C illustrates a wrap-around configuration. The sizes of the barriers might vary depending on the tooth size. Each illustrated barrier has a beaded rim 21, so as to provide a smoothed edge, which collars the crown-root junction of the tooth when surgically placed. The barriers are surgically implanted by conventional techniques and sutured in place by the use of body compatible sutures, such as GORE-TEX, a trademark of W. L. Gore & Associates, Inc.

The periodontal barrier of the present invention may incorporate microencapsulated chemotherapeutic agents into the body of the periodontal barrier in a variety of ways. In FIGS. 4A-4D there are illustrated cross-sectional views of alternate embodiments of barriers incorporating microencapsulated chemotherapeutic agents in accordance with the principles of the present invention. In particular, FIG. 4A depicts a cross-sectional view of a barrier according to the principles of the present invention, wherein one microencapsulated chemotherapeutic agent 30, such as an antibiotic, is incorporated into an inner layer 34 of the barrier. Conversely, another microencapsulated chemotherapeutic agent 30, such as an anti-inflammatory agent, is shown incorporated into an outer layer 28 of the barrier.

In FIG. 4B, a single incorporation of microencapsulated chemotherapeutic agents 30 may be placed between the outer 28 and inner 34 layers of the barrier. In FIG. 4C, the microencapsulated chemotherapeutic agents are disposed throughout the top layer 28 of the barrier. In addition, a thin elastomer coating 36 is placed over this outer layer. In FIG. 4D, one type of microencapsulated chemotherapeutic agent 30 is disposed in the inner layer 34 while a second type of microencapsulated chemotherapeutic agent 30 is disposed between the inner 34 and outer 28 layers. It will be appreciated that there are other ways the microparticles might be incorporated into the barriers.

As diagrammatically illustrated in FIGS. 5A through 5D, the time-release microparticles 30 can have a variety of shapes and sizes so as to provide the desired rate and timed release of the chemotherapeutic agents 32 contained therein. The outer wall or matrix of the microparticles 38 is composed of a material allowing for the controlled, sustained release of the chemotherapeutic agents over time upon diffusion through the material and/or degradation of the material.

The microparticles shown in FIGS. 5A through 5D are greatly enlarged, and in actual use, might typically be less than one millimeter in magnitude. As used herein, microparticles broadly include, without limitation, microspheres 40, microfibers or microfibrils 42, hollow microfibers 44, microsponges 46, as well as any other microshape which incorporate chemotherapeutic agents into their body or matrix.

In one embodiment, the microparticles are microspheres 40 having a spherical or near spherical shape as is generally illustrated in FIG. 5A, and are incorporated into the microstructure of the material comprising the periodontal barrier according to the present invention. For example, the microspheres can be contained within the mesh of fine fibrils connecting the matrix of nodes in expanded polytetrafluoroethylene (PTFE). In addition, somewhat larger microspheres can be meshed between layers of a multi-layered PTFE structure. The microspheres can be layered within the PTFE by adhesively positioning them onto the PTFE or by mixing them with a fluid or gel and flowing them into the netting or weave of the material. In yet another approach, microspheres can also be positioned between layers or coatings of the periodontal barrier 20 and between the barrier 20 and an elastomer coating 36 which might be covering the periodontal barrier.

In another embodiment, the microparticle may be in the form of microfibers or microfibrils 42 as is generally shown in FIG. 5B, which can be woven into the mesh of the periodontal barrier or, as described above, layered between successive layers of PTFE, or a similar material, comprising the periodontal barrier.

Alternatively, the microparticle may be in the form of a tubular member 44, or hollow microfiber, as is generally shown in FIG. 5C. As with microfibers or microfibrils, these hollow microfibers can be woven or layered into the body of the barrier.

In yet another embodiment, the microshapes may be in the form of microsponges, as is generally illustrated in FIG. 5D, which contain the desired chemotherapeutic agents within their own internal microchanneling.

Microspheres between 10 and 700 microns in diameter are preferred. Various chemical and physical methods for preparing microspheres have been developed over the past twenty-five years and are well known to those skilled in the art. In this regard, see for example Patrick B. Deasy, Microencapsulation and Related Drug Processes. Marcel Dekker Inc., New York, 1984. Coacervation, interfacial polymerization, solvent evaporation and spray drying are examples of methods used in the production of microspheres which incorporate chemotherapeutic agents. Similarly, microfibers or microfibrils can be obtained for layering or weaving into the barrier materials of the present invention. In this regard, hollow fibers ranging in size from 100 to 1,000 microns in diameter can be produced and drug loaded by extrusion.

A wide variety of chemotherapeutic agents can be incorporated into the microshapes employed according to the method of the present invention. For example, antibacterial agents such as the bisbiguanides, antibiotics such as vancomycin or tetracycline, anti-inflammatory agents such as indomethacin or hydrocortisone and tissue regenerative agents such as fibronectin may be employed, depending upon the particular treatment or regenerative goals sought.

Incorporation of the chemotherapeutic agents into the polymer comprising the microshape provides for a slow, sustained release of the chemotherapeutic agent. The polymer matrix or carrier material chosen is preferably biodegradable, pharmaceutically acceptable and available in various grades to allow for variable control of the release rate of different chemotherapeutic agents. In this regard, it will be appreciated that the biodegradable materials utilized in time release capsules taken orally or other suitable biodegradable materials safe for use in the body or commonly known may be employed. For example, various biocompatible polymers can be employed, including but not limited to, collagen, cellulosic polymers, ethylene vinyl acetate, methacrylate polymers, lactic-glycolic acid copolymers, polycaprolactone, etc. In addition, polymers such as polystyrene, polycarbonate, polysulfone, polylactides and polyurethane can be employed. It will be appreciated that nonbiodegradable polymers incorporating chemotherapeutic agents are also within the scope of the present invention.

Referring now to FIGS. 6A-6C, wherein is illustrated diagrammatic sectional views of alternative embodiments of microspheres in accordance with the present invention. The microspheres 40 have a polymer wall or shell 50 which surrounds the chemotherapeutic agent 32, or matrix containing the chemotherapeutic agent. Thus, the walls of the microspheres, as generally illustrated in FIGS. 6A through 6C, may have varying thicknesses and/or be made of a different material to provide for release of the agent continuously or periodically over an extended time period following surgical placement of the periodontal barrier. For example, a barrier may contain an antibiotic which would be released from one type of microparticle during the first critical days following surgery, whereas an anti-inflammatory agent contained in a second type of microparticle would be released for several weeks after implantation. In addition, it is to be understood that the chemotherapeutic agents contained within the microsphere may occur in any appropriate medium, such as aqueous, gelatinous, colloidal or semi-solid media.

Incorporation of an antibiotic, such as tetracycline, would help to minimize the infection potential and augment surgical healing. In addition, incorporation of anti-inflammatory agents, such as a nonsteroidal anti-inflammatory drug (e.g. flurbiprofen, meclofenamic acid, etc.) would help to minimize post-surgical swelling and discomfort. Moreover, a sustained, controlled delivery to the local site provides significant advantage over systemic dosages of these drugs. In addition, various chemotherapeutic agents can be positioned at different strategic areas of a periodontal barrier relative to their intended use. For example, an antibiotic could be positioned with the body of a periodontal barrier 20 for guided tissue regeneration, while an antiplaque agent could be positioned within the beaded rim of the barrier 21 which collars the crown-root junction of the tooth when surgically placed.

It will be further appreciated that the particular chemotherapeutic agents utilized as well as the dosages and durations of treatment will be in accordance with accepted treatment. The present invention addresses the manner in which the chemotherapeutic agents are delivered to the local treatment site.

Illustrated in FIGS. 7A through 7D, are various chemotherapeutic agent release patterns which might be achieved using the principles of the present invention. The charts shown illustrate quantity or dosage of the chemotherapeutic agent released over time. In FIG. 7A, three separate chemotherapeutic agents are illustrated as being released at three different substantially constant levels. For example, an antibiotic, anti-inflammatory and tissue regenerative agent may all be released at varying levels at the implantation site. In FIG. 7B, three different chemotherapeutic agents are released at different times. Thus, in accordance with the previous example, the antibiotic may be released first to control post-operative infection, followed by the anti-inflammatory agent to control swelling, and finally by a tissue regenerative agent to aid in healing. In FIG. 7C, a first chemotherapeutic agent is illustrated as being released very early in time and then a second chemotherapeutic agent is released at a substantially constant level for a sustained period of time. An initial high dose release of an antibiotic, followed by a sustained and lower release dose of an anti-inflammatory agent would be illustrative of such a pattern. Finally, FIG. 7D illustrates three different chemotherapeutic agents being released at different times. Such an impulse release pattern may prove particularly useful with a drug which exhibits toxic effects at sustained high dosages or whose efficacy diminishes if administered continuously over a sustained period of time.

It is to be understood, however, that even though numerous characteristics and advantages of the invention have been set forth in the foregoing description, together with details of the structure and function of the invention, the disclosure is illustrative only, and changes may be made in detail, especially in matters of shape, size and arrangement of parts within the principle of the invention, to the full extent indicated by the broad general meaning of the terms in which the appended claims are expressed.

Jernberg, Gary R.

Patent Priority Assignee Title
10004806, Jul 25 2001 PERIOVANCE, INC Periodontal regeneration composition and method of using same
10449151, Jul 10 2009 University of Pittsburgh - Of the Commonwealth System of Higher Education; Massachusetts Institute of Technology Artificial cell constructs for cellular manipulation
10456568, Mar 14 2013 HALLUX, INC. Method of treating infections, diseases or disorders of nail unit
10758329, Aug 20 2019 Hydrating mouth guard
11090363, Jul 10 2009 University of Pittsburgh - Of the Commonwealth System of Higher Education Vasoactive intestinal peptide release from microparticles
11413245, Jul 10 2009 University of Pittsburgh—Of the Commonwealth System of Higher Education; Massachusetts Institute of Technology Artificial cell constructs for cellular manipulation
11432959, Nov 20 2015 FORSIGHT VISION4, INC Porous structures for extended release drug delivery devices
11642310, Jan 29 2009 ForSight Vision4, Inc. Posterior segment drug delivery
5360341, Jul 30 1993 Method and appliance for promoting the healing of oral tissues
5455041, Sep 13 1993 RESEARCH FOUNDATION OF STATE UNIVERSITY OF NEW YORK AT BUFFALO, THE Method for inducing periodontal tissue regeneration
5607686, Nov 22 1994 United States Surgical Corporation Polymeric composition
5607689, Feb 22 1993 I Sugheri s.r.l. Latex element designed to achieve guided tissue regeneration in periodontal dental therapy
5727945, Aug 26 1996 Impregnated barrier and method of assisting bone or tissue regeneration
5814331, Nov 13 1995 Process for inhibiting pathogenic bacteria in the oral cavity and for binding peptide growth factors on surfaces
5939047, Apr 16 1996 Local delivery of chemotherapeutic agents for treatment of periodontal disease
5957690, Nov 17 1997 Textured high density PTFE medical barrier
6123957, Jul 16 1997 MEDICI LIFE SCIENCES LICENSING COMPANY LLC Delivery of agents and method for regeneration of periodontal tissues
6153210, Aug 14 1997 DEMEGEN, INC Use of locally delivered metal ions for treatment of periodontal disease
6155831, Mar 03 1999 Non-surgically retrievable guided tissue regeneration membrane
6319510, Apr 20 1999 Gum pad for delivery of medication to mucosal tissues
6328765, Dec 03 1998 W L GORE & ASSOCIATES, INC Methods and articles for regenerating living tissue
6409764, Dec 03 1998 W L GORE & ASSOCIATES, INC Methods and articles for regenerating bone or peridontal tissue
6531445, Mar 11 1991 Stryker Corporation Protein-induced morphogenesis in liver tissue
6576226, Nov 17 2000 Local delivery of agents for disruption and inhibition of bacterial biofilm for treatment of periodontal disease
6616698, Dec 14 1998 Warsaw Orthopedic, Inc Bone graft and guided bone regeneration method
6620406, Mar 08 1994 GENETICS INSTITUTE, LLC, FORMERLY KNOWN AS GENETICS INSTITUTE, INC Methods for treatment of periodontal diseases and lesions using bone morphogenetic proteins
6726898, Nov 17 2000 Local delivery of agents for disruption and inhibition of bacterial biofilm for treatment of periodontal disease
6955538, May 05 2000 DENTAL INOVA AS Equipment concerning the depot of medicament in the mouth
7105182, Jul 25 2001 PERIOVANCE, INC Periodontal regeneration composition and method of using same
7118376, Mar 14 2000 COLLDENT Y A LTD System for the controlled delivery of an active material to a dental site
7196056, Mar 11 1991 Stryker Corporation Protein-induced morphogenesis of kidney tissue
7314375, Jan 12 2001 Henkel KGaA Provisional dental implant for preparing an alveolus
7322825, Jul 25 2001 PERIOVANCE, INC Method of treating periodontal disease using periodontal regeneration composition
7819918, Jul 16 2001 Depuy Synthes Products, LLC Implantable tissue repair device
7871440, Dec 11 2006 Depuy Synthes Products, LLC Unitary surgical device and method
7939108, Dec 14 2000 Warsaw Orthopedic, Inc Method of making demineralized bone particles
7959941, Oct 12 2001 Warsaw Orthopedic, Inc Bone graft comprising a demineralized bone matrix and a stabilizing agent
8002813, Oct 15 1999 Warsaw Orthopedic, Inc Volume maintaining osteoinductive/osteoconductive compositions
8197474, Oct 15 1999 Warsaw Orthopedic, Inc. Volume maintaining osteoinductive/osteoconductive compositions
8268008, Jun 11 2003 Warsaw Orthopedic, Inc Osteoimplants and methods for their manufacture
8287277, Aug 08 2007 COLLDENT Y A LTD Reshapable device for fixation at a dental site
8313328, Jul 25 2001 PERIOVANCE, INC Periodontal regeneration composition and method of using same
8529962, Dec 14 2000 Warsaw Orthopedic, Inc Method of making demineralized bone particles
8545864, Nov 02 2005 Warsaw Orthopedic, Inc Hemostatic bone graft
8556989, Sep 22 2003 OSTEOGENICS BIOMEDICAL, INC Hydrophilic high density PTFE medical barrier
8556990, Feb 23 2009 OSTEOGENICS BIOMEDICAL, INC Reinforced PTFE medical barriers
8663672, Jul 19 2000 Warsaw Orthopedic, Inc Osteoimplant and method of making same
8721735, Feb 14 2005 OSTEOGENICS BIOMEDICAL, INC PTFE composite multi-layer material
8722075, Oct 24 2008 Warsaw Orthopedic, Inc Compositions and methods for promoting bone formation
8753689, Dec 14 2001 Warsaw Orthopedic, Inc. Method of making demineralized bone particles
8846098, Jul 10 2009 University of Pittsburgh - Of the Commonwealth System of Higher Education; Massachusetts Institute of Technology Artificial cell constructs for cellular manipulation
9375558, Mar 14 2013 HALLUX, INC. Method of treating infections, diseases or disorders of nail unit
9387094, Jul 19 2000 Warsaw Orthopedic, Inc Osteoimplant and method of making same
9393116, Jun 11 2003 Warsaw Orthopedic, Inc. Osteoimplants and methods for their manufacture
9498612, Mar 14 2013 HALLUX, INC Method of treating infections, diseases or disorders of nail unit
9668844, Nov 06 2013 COLLDENT Y A LTD Device for fixation at a dental site
9757339, Jul 10 2009 University of Pittsburgh - Of the Commonwealth System of Higher Education; Massachusetts Institute of Technology Artificial cell constructs for cellular manipulation
9999520, Jul 19 2000 Warsaw Orthopedic, Inc. Osteoimplant and method of making same
RE37382, Dec 10 1998 Gum pad for mucosal delivery of medication
Patent Priority Assignee Title
4226848, Mar 02 1979 Teijin Limited Method and preparation for administration to the mucosa of the oral or nasal cavity
4249531, Dec 27 1972 ALZA Corporation Bioerodible system for delivering drug manufactured from poly(carboxylic acid)
4292299, Nov 06 1978 Teijin Limited Slow-releasing medical preparation to be administered by adhering to a wet mucous surface
4321711, Oct 18 1978 SUMITOMO ELECTRIC INDUSTRIES, LTD Vascular prosthesis
4536387, Feb 12 1982 Unitika Ltd Anti-cancer device
4568536, Feb 08 1985 Ethicon, Inc. Controlled release of pharmacologically active agents from an absorbable biologically compatible putty-like composition
4650665, Feb 08 1985 Ethicon, Inc. Controlled release of pharmacologically active agents from an absorbable biologically compatible putty-like composition
4657548, Sep 11 1984 COLLA-TEC, INC , A CORP OF DE Delivery system for implantation of fine particles in surgical procedures
4685883, Sep 12 1983 Local delivery of chemotherapeutic agents for the treatment of periodontal disease
4703108, Mar 27 1984 University of Medicine & Dentistry of New Jersey Biodegradable matrix and methods for producing same
4713243, Jun 16 1986 JOHNSON & JOHNSON CONSUMER PRODUCTS, INC Bioadhesive extruded film for intra-oral drug delivery and process
4745161, Apr 10 1985 Ceskoslovenska akademie ved Soluble and biodegradable polyamino acid activated for bonding of biologically active compound
4752294, Nov 07 1984 SUNSTAR LAUSANNE SA Element for controlled growth into surgically intervened areas
4764377, Oct 07 1983 The Forsyth Dental Infirmary for Children Intra-pocket drug delivery devices for treatment of periodontal diseases
4776890, Dec 18 1985 ANGIOTECH BIOMATERIALS CORPORATION Preparation of collagen hydroxyapatite matrix for bone repair
4780320, Apr 29 1986 TECHNICAL CHEMICALS AND PRODUCTS, INC, Controlled release drug delivery system for the periodontal pocket
4789662, Dec 23 1985 PIERRE FABRE MEDICAMENT, 125 RUE DE LA FAISANDERIE 75116 PARIS, FRANCE A CORP OF FRANCE Method for the treatment of periodontal pockets with a composition comprising collagen and an antiseptic or anti-inflammatory substance
4789663, Jul 06 1984 COHESION TECHNOLOGIES, INC Methods of bone repair using collagen
4795467, Mar 28 1985 NEUCOLL, INC Xenogeneic collagen/mineral preparations in bone repair
4804744, Jan 04 1984 Biomet, Inc; Biomet Manufacturing Corp Osteogenic factors
4816339, Apr 28 1987 Edwards Lifesciences Corporation Multi-layered poly(tetrafluoroethylene)/elastomer materials useful for in vivo implantation
4828563, Jun 18 1985 DR MULLER-LIERHEIM AG, BEHRINGSTRASSE 6, 8033 PLANEGG, WEST GERMANY Implant
4837285, Mar 27 1984 MediMatrix Collagen matrix beads for soft tissue repair
4839175, Jul 28 1986 LIPOSOME TECHNOLOGY, INC , A CORP OF DE Liposomes with enhanced retention on mucosal tissue
4841962, Mar 27 1984 MEDIMATRIX INCORPORATED Collagen matrix/polymer film composite dressing
4892516, May 07 1982 HARLE, ANTON, Surgical aid
4961707, Dec 22 1987 UNIVERSITY OF FLORIDA, 207 TIGERT HALL, GAINESVILLE, FL 32611, A CORP OF FL Guided periodontal tissue regeneration
5032445, Jul 06 1984 W L GORE & ASSOCIATES, INC Methods and articles for treating periodontal disease and bone defects
5077049, Jul 24 1989 TOLMAR, INC Biodegradable system for regenerating the periodontium
EP3060463,
GB146525A,
SU353724,
WO8600517,
WO8700272,
WO9013302,
WO9110696,
/
Executed onAssignorAssigneeConveyanceFrameReelDoc
Feb 20 1992Gary R., Jernberg(assignment on the face of the patent)
Date Maintenance Fee Events
Feb 27 1996ASPN: Payor Number Assigned.
Sep 27 1996M283: Payment of Maintenance Fee, 4th Yr, Small Entity.
Oct 17 1996SM02: Pat Holder Claims Small Entity Status - Small Business.
Aug 30 2000M284: Payment of Maintenance Fee, 8th Yr, Small Entity.
Aug 25 2004M2553: Payment of Maintenance Fee, 12th Yr, Small Entity.
Sep 10 2004ASPN: Payor Number Assigned.
Sep 10 2004RMPN: Payer Number De-assigned.


Date Maintenance Schedule
Mar 30 19964 years fee payment window open
Sep 30 19966 months grace period start (w surcharge)
Mar 30 1997patent expiry (for year 4)
Mar 30 19992 years to revive unintentionally abandoned end. (for year 4)
Mar 30 20008 years fee payment window open
Sep 30 20006 months grace period start (w surcharge)
Mar 30 2001patent expiry (for year 8)
Mar 30 20032 years to revive unintentionally abandoned end. (for year 8)
Mar 30 200412 years fee payment window open
Sep 30 20046 months grace period start (w surcharge)
Mar 30 2005patent expiry (for year 12)
Mar 30 20072 years to revive unintentionally abandoned end. (for year 12)